Anti-Fab Aptamers for Shielding Virus from Neutralizing Antibodies

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• 作者：Darija Muharemagic ; Mahmoud Labib ; Shahrokh M. Ghobadloo ; Anna S. Zamay ; John C. Bell ; Maxim V. Berezovski
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：October 17, 2012
• 年：2012
• 卷：134
• 期：41
• 页码：17168-17177
• 全文大小：580K
• 年卷期：v.134,no.41(October 17, 2012)
• ISSN：1520-5126

文摘

Oncolytic viruses are promising therapeutics that can selectively replicate in and kill tumor cells. However, repetitive administration of viruses provokes the generation of neutralizing antibodies (nAbs) that can diminish their anticancer effect. In this work, we selected DNA aptamers against the antigen binding fragment (Fab) of antivesicular stomatitis virus polyclonal antibodies to shield the virus from nAbs and enhance its in vivo survival. For the first time, we used flow cytometry and electrochemical immunosensing to identify aptamers targeting the Fab region of antibodies. We evaluated the aptamers in a cell-based infection assay and found that several aptamer clones provide more than 50% shielding of VSV from nAbs and thus have the potential to enhance the delivery of VSV without compromising the patient鈥檚 immune system. In addition, we developed a bifunctional label-free electrochemical immunosensor for the quantitation of aptamer-mediated degree of shielding and the amount of vesicular stomatitis virus (VSV) particles. Electrochemical impedance spectroscopy was employed to interrogate the level of VSV in a linear range from 5 脳 10⁴ to 5 脳 10⁶ PFU mL^鈥? with a detection limit of 10⁴ PFU mL^鈥?.